The antiviral agent cidofovir [(S)-1-(3-hydroxy-2-phosphonyl-methoxypropyl)cytosine] has pronounced activity against nasopharyngeal carcinoma grown in nude mice.
The effect of the antiviral agent (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (cidofovir) on the EBV-associated tumor nasopharyngeal carcinoma (NPC) was evaluated in NPC xenografts in athymic mice. Intratumoral injection arrested tumor growth within 1 week, and by 4 weeks, tumors regressed to 8-75% (39 +/- 33%) of the original size, whereas control tumors injected with PBS grew to 282 +/- 25% of the original size. Ganciclovir slowed but did not arrest or cause regression of tumor growth. A striking antitumor effect was also produced by systemic administration; at 4 weeks, tumors were 79 +/- 49% of the original size, compared with 635 +/- 91% for the controls. Widespread apoptosis was detected after treatment for 2-6 days in C15 as well as two other NPC xenografts, C17 and C18; the latter NPCs have mutations in the p53 gene. These data indicate that cidofovir induces rapid cell death through apoptosis in EBV-transformed epithelial cells.
Neyts
J
J
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill 27599-7295, USA.
Sadler
R
R
De Clercq
E
E
Raab-Traub
N
N
Pagano
J S
JS
D000293:Adolescent; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000821:virology; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004354:Drug Screening Assays, Antitumor; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology / Q000627:therapeutic use; D016158:Genes, p53; D006566:Herpesviridae Infections / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000472:pathogenicity; D006801:Humans; D015552:Injections, Intralesional; D051379:Mice; D008819:Mice, Nude; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000821:virology; D009368:Neoplasm Transplantation; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D014412:Tumor Virus Infections / Q000188:drug therapy* / Q000473:pathology / Q000821:virology
D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir; D015774:Ganciclovir